It is well known that the use of radiopharmaceuticals injected in the body of the patient is an essential tool in medical diagnostic and in particular in the diagnostic of tumours. Gamma scintigraphy, also named Single Photon Emission Tomography (SPET or SPECT), is the most common technique. But, in the past fifteen years, Positron Emission Tomography (PET) has spread quickly also in association with the quantitative observation of the morphology of internal organs allowed by Computerized Tomography (CT). The future of tumor diagnostic is in the use of combined devices as CT/PET and also MRI/PET (MRI=Magnetic Resonance Imaging).
These widespread diagnostic methods employ radioisotopes distributed by specialized companies and produced in nuclear reactors (Tc-99m is used for SPET) and by high current cyclotrons (F-18 is the most used isotope in PET diagnostics). Many hospitals run cyclotrons to produce locally the needed isotopes. These and other isotopes used for SPET and PET are listed in Table 1 and 2. The proton energy range is also indicated in MeV (million electron-volt).
TABLE 1Radio-isotopes used in SPETProton energyIsotopeHalf lifeDecayrange [MeV]Utilization51Cr27.7 daysγ 2-30Tomo-scintigraphy67Ga3.3 daysγ14-33Tomo-scintigraphy oflymphomas111In 2.8 daysγ13-31Tomo-scintigraphy ofendocrine tumours123I13.2 hoursγ13-30Tomo-scintigraphy201Tl72.9 hoursγ20-40Tomo-scintigraphy
TABLE 2Radio-isotopes used in PETProton energyIsotopeHalf lifeDecayrange [MeV]Utilization11C20.4 minβ+6-25Indicator of cellularactivity15O 2.1 minβ+5-21Indicator of tumournecrosis18F 109 minβ+3-20Metabolism of theglucose81Rb 4.6 hoursβ+>20Myocardium and brain
Others radiopharmaceuticals introduced in the body of patients (brachitherapy) are used for pain palliation and the control of primary tumours and methastases. Some of the most common and/or promising ones, which can be produced with proton beams, are listed in Table 3.
TABLE 3Radio-isotopes produced for palliation and tumour cure.Proton energyIsotopeHalf lifeDecayrange [Mev]Utilization67Cu61.9 hoursβ−8-33Radio-immuno therapy153Sm46.5 hoursβ−>15Cure and pain relieve ofbony metastases165Er10.4 hourse−6-25Radio-immuno therapy166Ho26.8 hoursβ−, γ(*)Treatment metastasesand skin melanoma186Re90.6 hoursβ−, γ(*)Cure and pain relieve ofbony metastases212Bi60.6 minα(**)Radio immuno therapy213Bi45.6 minα(**)Radio immuno therapy(*) These isotopes can be produced with the ‘Adiabatic Resonance Crossing’ technique described in WO98/59347.(**) In hospitals these isotopes are usually produced with generators bought from specialized companies but they could also be produced with 30 MeV cyclotrons.
Brachitherapy is today less common than the above said diagnostic techniques, but rapid developments are foreseen due to the availability of many isotopes, with different production mechanisms and various half-lives.
The production of many of the radioisotopes, listed as examples in Tables 1-3, requires intense proton beams of energies larger than the 10-15 MeV used for the production of the standard PET isotopes, F-18. Moreover, the production cross sections of nearly all the isotopes increase with energy so that, for a fixed proton current, the production rate increases with the energy and the use of higher energies is convenient if the simultaneous increase of the production of undesired radioisotopes can be avoided. In all cases the currents needed for these applications are at least fifty microampere.
For this reason the said high-current proton beams are valid tools in diagnostic and tumour brachytherapy. On the other hand, collimated proton beams of higher energy (up to 250 MeV) but much lower currents (nanoamperes) are used in ‘protontherapy’, the precision radiation therapy used also for deep seated tumours. This is the most common type of ‘hadrontherapy’ because it spares the healthy tissues surrounding the tumour much better than the ‘X-rays’ produced by 5-20 MeV electron linacs while having practically the same radiobiological and clinical effects. It is not necessary to perform many clinical trials to reach the conclusion that—since the proton dose distribution is, in all cases, more localized on the tumour target—this modality is always more favourable than the conventional ones for solid tumours located close to the organs at risk that do not have to be irradiated. The only limitations are due to the needed investments and the dimensions of the equipments which imply a treatment cost higher by a factor 2-3.
Today, on a population of 10 million inhabitants, approximately 20,000 patients are irradiated every year with X-rays. Recent studies performed in many countries have reached the conclusion that between 12% to 15% of these patients treated with protons rather than with X-rays would have such a therapeutic advantage to justify the higher cost.
From the previous considerations it is clear that proton beams produced for modern diagnostic and for therapeutic medicine need to fulfill different requirements and therefore require different proton accelerators:    1. for producing radioisotopes the energy range is 10-70 MeV and the current range is 50-1000 μA,    2. for protontherapy the energy range is 60-250 MeV and the current range is 0.1-10 nA.
Mostly cyclotrons—but occasionally also linacs—are used to accelerate protons and other types of ions for the production of radioisotopes. For protontherapy, both cyclotrons (room-temperature or super-conductive) and synchrotrons are used. Even belonging to the same hospital or centre, these accelerators are usually installed in separate buildings and are managed separately, typically the first by nuclear physicians, chemists and nuclear physicists and the second ones by radiation oncologists and medical physicists.